ClinVar Miner

Submissions for variant NM_000117.3(EMD):c.110A>T (p.Lys37Met)

gnomAD frequency: 0.00003  dbSNP: rs1085307681
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489349 SCV000577026 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing The K37M variant in the EMD gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The XX variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K37M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret K37M as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001058405 SCV001222971 uncertain significance X-linked Emery-Dreifuss muscular dystrophy 2023-03-20 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 37 of the EMD protein (p.Lys37Met). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EMD protein function. ClinVar contains an entry for this variant (Variation ID: 426553). This variant has not been reported in the literature in individuals affected with EMD-related conditions. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002431430 SCV002744700 uncertain significance Cardiovascular phenotype 2019-08-10 criteria provided, single submitter clinical testing The p.K37M variant (also known as c.110A>T), located in coding exon 2 of the EMD gene, results from an A to T substitution at nucleotide position 110. The lysine at codon 37 is replaced by methionine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001834587 SCV002084672 uncertain significance Emery-Dreifuss muscular dystrophy 2020-12-29 no assertion criteria provided clinical testing

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